Impact of type 2 diabetes on the relationship between chronic kidney disease and cardiovascular outcomes in heart failure across ejection fraction: observational study from the Swedish heart failure and the Swedish National diabetes registries

Abstract Background Chronic kidney disease (CKD) is a risk factor for cardiovascular (CV) events in patients with heart failure (HF). It is unclear whether type 2 diabetes (T2D), closely intertwined with both HF and CKD, modifies the association between cardiovascular outcomes and CKD in HF patients, and whether this association differs according to ejection fraction (EF). Methods HF patients enrolled in the Swedish Heart Failure Registry from January 2017 to December 2021 were analyzed. Linkage with the National Diabetes Registry and other population registries provided extensive baseline information. Patients were stratified by T2D status and CKD stages, defined by estimated glomerular filtration rate (eGFR: <30, 30–44, 45–59, ≥ 60 ml/min/1.73 m2). The primary outcome was the composite of time to first HF hospitalization (HHF) or CV death. Secondary outcomes were major adverse CV events (MACE, i.e. CV death, non-fatal myocardial infarction and stroke), CV death and all-cause death. Multivariable Cox regression models assessed the associations between eGFR and outcomes according to T2D, including interaction testing. A subgroup analysis was conducted by EF. Results Of 36,597 patients included, 8,053 (22%) had T2D, 23,562 (64.4%), 7122 (19.4%), 4477 (12.2%), 1436 (4.0%), were in the four eGFR categories (eGFR ≥ 60, 45–59, 30–44, and < 30 mL/min/1.73 m2, respectively), and 53%, 25%, 22% had HF with reduced, mildly-reduced, and preserved EF, respectively. Across eGFR, patients with vs. without T2D were younger, more often male, with higher CV comorbidity and more frequent use of cardio-renal drugs. Across EF categories, T2D patients had higher prevalence of CKD. Lower eGFR categories were progressively associated with higher risk of the primary outcome, independently of T2D. This was consistent across EF, except in HFpEF with eGFR < 30 ml/min/1.73 m2, where the magnitude of the association in T2D group was smaller than in non-T2D (p-interaction < 0.01). Risks of MACE, CV death and all-cause mortality were higher for lower eGFR categories, with lower hazards in T2D group (p-interaction < 0.01). Conclusions In a contemporary HF cohort, decreased kidney function was associated with a progressively higher risk of HHF/CV death, and T2D was not a risk modifier. Renal protection should therefore be implemented in HF regardless of T2D.